The long-term survival of baboon-to-monkey kidney and liver xenografts

Robert Zhong*, Jane Tucker, Zheng Zhang, William Wall, David Grant, Douglas Quan, Bertha Garcia, Zu Hua Gao, Sami Asfar, Michael Sharpe, Adrian Gelb, Michele Bailey, Calvin Stiller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The present study was undertaken to develop an optimum immunosuppressive regimen in baboon-to-monkey life-supporting kidney xenografts. Baseline therapy for all groups include cyclosporine (CsA) and steroids. We compared adding (1) cyclophosphamide (CyP) at dose of 20 mg/kg/day given on post-operative day (POD) 0, 2, 5 and 7; (2) mycophenolic mofetil (MMF) at a dose of 40 mg/kg/day by daily gavage; or (3) CyP + rapamycin (Rap). The latter group was divided into high and low dose subgroups. Untreated xenografts were rejected on POD 6, CsA alone treated xenografts survived for 35 days and CsA + CyP treated xenografts survived for 45 days. Adding MMF significantly prolonged mean survival to 111 ± 53 days, but the xenografts eventually developed rejection. Combination therapy including CsA, CyP and Rap reliably prevented xenogenic rejection and achieved a mean survival of 290 ± 30 days. However, high dose CyP + Rap led to high incidence of post-transplant lymphoproliferation disorders (PTLD), while the incidence of PTLD was significantly less in the low dose subgroup (P < 0.01). Four animals in this subgroup survived for more than 300 days with normal renal function and histology. In addition, two liver recipients treated with CsA + CyP survived for 91 and 1076 days. We conclude that long-term survival of kidney or liver xenografts can be achieved in a non-human concordant xenograft model using currently available immunosuppressive agents.

Original languageEnglish (US)
Pages (from-to)398-409
Number of pages12
JournalXenotransplantation
Volume10
Issue number5
DOIs
StatePublished - Sep 2003

Keywords

  • Baboon
  • Kidney
  • Liver
  • Monkey
  • Rejection
  • Xenotransplantation

ASJC Scopus subject areas

  • Immunology
  • Transplantation

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